Potency estimation of vaccine batches remains unaffected by anesthesia for intracerebral injection
ABSTRACT Potency testing of rabies and whole-cell pertussis vaccine batches is still performed by an intracerebral (i.c.) challenge test, in conformity with international regulatory requirements. For the i.c. injection, the use of anesthesia is strongly recommended to alleviate the severe pain induced by the procedure. Today, anesthesia is not consistently mentioned in regulatory requirements, in contrast to the times when the potency tests were developed. The introduction of anesthesia is hampered, due to the lack of data on a hypothetical impact of anesthesia on potency estimation. Here, we show the comparative analysis of the extensive batch release data set of a rabies vaccine for human use that was tested in two laboratories of which only one applied anesthesia. In essence, we find that the mean batch test results were similar to each other, demonstrating that anesthesia for i.c. injection does not interfere with potency estimation. Consequently, we recommend the update of regulatory requirements and protocols and support the implementation of anesthesia for i.c. injection.
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ABSTRACT: The use of X-ray photography following injection of iophendylate to verify that intraventricular injections in mice have been satisfactorily accomplished is misleading since it fails to detect leakage into the periphery. Radioactive labelling reveals that a substantial proportion of the injected material is rapidly carried to the periphery in the bloodstream.British Journal of Pharmacology 05/1974; 50(4):603-5. DOI:10.1111/j.1476-5381.1974.tb08596.x · 4.99 Impact Factor
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ABSTRACT: 9 laboratories from 7 countries including both laboratories from the public and private sector participated in a collaborative study organised under the aegis of the European Directorate for the Quality of Medicines Biological Standardisation Programme in order to establish batch 4 of the European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for rabies vaccine (inactivated) for veterinary use. Establishment of Ph. Eur. BRP batch 4 was necessary in order to replace Ph. Eur. BRP batch 3, the stocks of which were dwindling. 8 laboratories provided results. Ph. Eur. BRP batch 4 was calibrated against the 5th International Standard for inactivated rabies vaccine in International Units (IU) using the vaccination challenge method of the Ph. Eur. monograph 0451. The International Standard (IS), Ph. Eur. BRP batch 4 and batch 3 are all freeze-dried vaccines prepared by beta-propiolactone inactivation of the Pitman Moore strain of rabies. Based on the results of the study, a potency of 11 IU/vial was assigned to Ph. Eur. BRP batch 4 for rabies vaccine (inactivated) for veterinary use. Nevertheless, it was noted that the vaccination challenge assay used as the "golden standard" for potency determination of inactivated rabies vaccines for veterinary use is a crude assay requiring the use of a large number of animals. Evidence from this study and from the collaborative study to establish Ph. Eur. BRP batch 3 suggests that the assay is difficult to perform and provides highly variable results. The validation of a suitable in vitro alternative is therefore highly recommended, as is the possible improvement of the in vivo assay, which will most likely remain the "golden" standard.Pharmeuropa bio / the Biological Standardisation Programme, EDQM 01/2005; 2004(1):17-22.
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ABSTRACT: All inactivated rabies vaccines for veterinary use produced in France are tested for potency before their release on the market. The potency is determined using the vaccination challenge method on mice as required by the European Pharmacopoeia (Eur. Phar.) monograph 0451, which is derived from the NIH test. Although it is considered as the “golden standard”, this in-vivo test remains quite difficult to perform due to its variability and the strict validation process required by the Eur. Phar. monograph. During the last 2 years, theour laboratory has tested 122 batches of veterinary rabies vaccines. More than 99% of rabies vaccines were found in compliance with the requirements, i.e with a potency exceeding 1 IU/dose. However this retrospective analysis demonstrates and confirms the difficulty to obtain a fully valid ated assay. It reveals that the validation of the totality of criterions was obtained for for all assays performed only 42% of assays met all validity criteria, even iif severe invalid assays ncluding assays that arewere repeated. The present study also reveals that some criterions criteria are recurrently involved in the invalidation of assays. The data reported here, together with the data of other Official Medicines Control Laboratories (OMCL), should be used as a basis to refine and reconsider the validation criteriaprocess of potency tests for rabies vaccines potency tests.Pharmeuropa bio & scientific notes 10/2008; 20(4):655-664.